The principal goal of this project is to elucidate the structure and biological significance of an insulin-like protein in human serum. This protein has been purified from bank blood plasma and chemically characterized. It is presently termed the nonsuppressible insulin-like protein (NSILP) to distinguish it from insulin and smaller molecular weight peptides possessing growth promoting activity. NSILP is a 90,000 mol. wt. glycoprotein with a sedimentation coefficient of 4.72S. It is remarkably similar to transferrin and haptoglobin 1-1, but amino acid analysis clearly distinguishes it by its high arginine and tryptophan content. An immunoassay for NSILP has been developed that reveals a normal human serum concentration of 2-4 micro g/ml. Additional antiserum studies verified that NSILP comprised 85-95% of the total serum NSILA. Fat cell receptor studies demonstrated that NSILP and insulin did not compete for the same receptor; instead, a positive is directed at characterizing the significance of the physiological interaction between insulin and NSILP. BIBLIOGRAPHIC REFERENCES: Poffenbarger, P.L., T. Pozefsky, and J.S. Soeldner. 1976. The direct relationship of proinsulin-insulin hypersecretion to basal serum levels of cholesterol and triglyceride in myotonic dystrophy. J. Lab. Clin. Med. (in press). Poffenbarger, P.L., R. Burns, and A. Bennett-Novak. 1976. A phylogenetic study of serum nonsuppressible insulin-like activity (NSILA). Comp. Biochem. Physiol. 52A:223-226.